Preclinical Oncology: 2020 Spotlight Roundup
2020 has been a year like no other! During this unprecedented period, we worked hard to bring new models and technologies on board to help enable relevant approaches for your preclinical oncology and immuno-oncology drugs.
An area of continuing growth in the industry has been humanized mouse models. At Covance, we have established a platform using human PBMCs and demonstrated proof of concept in the A549 human non-small cell lung carcinoma and the Mia-PaCa-2 human pancreatic models for both baseline growth and response to pembrolizumab:
- Modeling immuno-oncology in a humanized mouse:https://www.covance.com/industry-solutions/oncology/preclinical/tumor-spotlights/modeling-immuno-oncology-in-a-humanized-mouse.html
- Update on the preclinical use of human PBMC for immuno-oncology modeling: https://www.covance.com/industry-solutions/oncology/preclinical/tumor-spotlights/update-on-the-preclinical-use-of-hPBMC-for-immuno-oncology-modeling.html
Work on this platform continues as we investigate immune cell responses following treatment with pembrolizumab by flow cytometry.
Another area of exponential growth in our industry has been in the adoptive cell therapy space. To support this sector, our extensive list of human xenograft cell lines (https://www.covance.com/industry-solutions/oncology/preclinical/complete-cell-line-list.html) provides customers with an array of options for both hematologic malignancies and solid tumors. Having the models, however, is only the first step. We have in vivo growth data on more than 30 of these models in the relevant NSGTM mouse strain and we have approximately 100 cell lines that are luciferase enabled. In order to track and monitor in vivo tumor burden and response to therapy, we have industry leading capabilities in bioluminescence imaging (BLI). In being the first CRO to offer BLI, we have the longest experience, the most relevant models and unsurpassed expertise in this field as we highlighted in a 2020 Spotlight:
Bioluminescence imaging: In vivo monitoring of tumor development, disease dissemination and treatment efficacy: https://www.covance.com/industry-solutions/oncology/preclinical/tumor-spotlights/Bioluminescence-imaging-spotlight.html
If you need support running a study with BLI imaging reach out today!
While having the appropriate model is critical, it’s equally important to have the capabilities required for phenotypic and mechanistic evaluation of therapeutic responses. These phenotypic and mechanistic biomarkers help define actions and outcomes of novel therapies being investigated. This year we expanded our menu of off-the-shelf flow cytometry packages and panels to include more in-depth capabilities around phenotypic analysis of both lymphoid and myeloid populations along with functional analysis of tumor infiltrating leukocytes and CAR T cell persistence in vivo.
To date, we have roughly 20 ready-to-go flow cytometry panels and/or packages that span human and mouse cell types and helps solidify our best-in-class preclinical flow cytometry services.
- Determining preclinical CAR T-cell persistence by flow cytometry
- Functional Analysis of Tumor Infiltrating Lymphocytes by Flow Cytometry Using the Cytokine/Cytotoxicity™ Panel
- Measuring Tumor Antigen-Specific Immunity Through ELISpot and FluoroSpot
In another growing area of in vitro capabilities, 2020 saw our launch of an in vitro tumor platform that utilizes zPREDICTA®s organ-specific three-dimensional (3D) culture models. These assays support long-term culture of tumor cells within relevant physiologic extracellular matrix components that have been shown to be critical in maintaining the tumor microenvironment as well as maintaining specific tumor phenotypes. Information around the establishment of the reconstructed bone marrow (r-Bone) 3D platform to support hematologic malignancies or other cancers that home to the bone was highlighted during 2020:
A New Covance Offering: zPREDICTA®s Reconstructed Bone (r-Bone), plate-based, 3-dimensional (3D) culture assay that mimics the tumor microenvironment found in myeloma, acute myelogenous leukemia and solid tumor metastasis: https://www.covance.com/industry-solutions/oncology/preclinical/tumor-spotlights/reconstructed-bone-3d-model.html
Finally, it wouldn’t be a complete year without bringing some new models onboard or highlighting some of our tried and true models. To this end we shared data and insights on our continued efforts to develop relevant syngeneic orthotopic models:
Pan02-Luc: An orthotopic model of pancreatic cancer: https://www.covance.com/industry-solutions/oncology/preclinical/tumor-spotlights/pan02-luc-an-orthotopic-model-of-pancreatic-cancer.html
CT26-Luc: An orthotopic murine model of colon cancer: implications for immuno-oncology studies: https://www.covance.com/industry-solutions/oncology/preclinical/tumor-spotlights/ct26-luc-an-orthotopic-murine-model-of-colon-cancer-implications-for-immuno-oncology-studies.html
Syngeneic orthotopic models is an active area of development for us so stay tuned in 2021 to hear more about these approaches or reach out today to learn more from one of our scientists. Aside from syngeneic models, we also focused efforts on reestablishing the human BT474 breast model in the NSGTM mouse strain. This model has been notoriously difficult to work with but has seen a renewed interest in the past few years. See how we approached this in our Model Spotlight during 2020:
BT-474 Human ductal breast carcinoma: New life for an old model: https://www.covance.com/industry-solutions/oncology/preclinical/tumor-spotlights/bt-474-human-ductal-breast-carcinoma.html
As we embark on 2021, we aim to continue our pursuit of bringing on additional models and assays to help you advance your novel oncology and immuno-oncology assets. There are many ongoing initiatives that will come to fruition during 2021 and, as always, we look to the future for approaches to continue expanding our preclinical oncology and immuno-oncology solutions for your drug discovery and development needs.
All animal work in the relevant Spotlights was approved by the site Institutional Animal Care and Use Committee and was performed in conformance with the Guide for the Care and Use of Laboratory Animals within an AAALAC-accredited program with humane euthanasia criteria predetermined on all studies.
We’d love to hear from you. Tell us what you’re looking for and how we can help support you in your drug development process!
Maryland Franklin, PhD | Executive Director, Scientific Development